Assisted Hatching for in Vitro Fertilization-Embryo Transfer: An

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Review Article Open Access Assisted Hatching for In Vitro Fertilization-Embryo Transfer: An Update Shahryar K Kavoussi* Austin Fertility & Reproductive Medicine/Westlake IVF, 300 Beardsley Lane, Bldg B, Suite 200, Austin, Texas, USA *Corresponding author: Shahryar K Kavoussi, M.D, M.P.H, Austin Fertility & Reproductive Medicine/Westlake IVF, 300 Beardsley Lane, Bldg B, Suite 200, Austin, Texas, USA, Tel: 001-(512) 444-1414; Fax: 001-(512) 444-5621; E-mail: [email protected] Received date: 06-02-2014; Accepted date: 13-03-2014; Published date: 17-03-2014 Copyright: © 2014 Kavoussi SK. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Assisted Hatching (AH) is a technique performed after In Vitro Fertilization (IVF) and involves the artificial thinning or opening of the Zona Pellucida (ZP) prior to Embryo Transfer (ET) as an attempt to improve the probability of embryo implantation. AH can be performed by embryologists via mechanical, chemical, or laser-assisted means. A few studies suggest that a larger size of ZP opening/thinning as well as a site near the ICM may be associated with a greater probability for complete hatching. It is not recommended to apply AH to all IVF cycles universally. Subgroups of patients that may benefit from AH include those with prior implantation failure, those undergoing Frozen-Thawed Embryo Transfer (FET) cycles, and women who are 38 years of age or older. IVF programs should identify subgroups of women within their patient population who may benefit clinically from AH.

Keywords: Embryo; Blastocyst; Assisted hatching; Zona pellucida cleavage stage ET; LAH was performed at the expanded blastocyst stage. The Pregnancy Rates (PR), Implantation Rates (IR), and Live Introduction Birth Rates (LBR) were higher in the group with 50% ZP opening (74%, 52%, 65%) when compared with the control group (17%, 10%, In utero, as an embryo at the blastocyst stage expands and thins its 13%; P<0.01) and the group with 40μm ZP opening (43%, 27%, 38%; surrounding glycoprotein covering, the Zona Pellucida (ZP), rupture P<0.04) [3]. The same authors conducted a study in order to examine of the ZP eventually occurs with the aid of proteases known as lysins. the effect of the size of ZP thinning on clinical outcomes in vitrified- The embryo hatches and begins the implantation process via warmed cleavage stage FET. Random assignment of 120 cases was interaction with endometrial cells. The inefficiency of Implantation made to 50% ZP thinning and 25% ZP thinning groups. Clinical Rates (IR) after Embryo Transfer (ET) may be attributed to various Pregnancy Rates (CPR) (46.7 vs 25.0%; P=0.0218) and IR (32.0 vs factors including the potential failure of a euploid blastocyst to hatch 16.2%, P=0.0090) were significantly increased in the 50% ZP thinning from the ZP. Assisted Hatching is a technique performed after in vitro group [4]. Zhang et al. studied the effect of the size of ZP thinning by fertilization and involves the artificial thinning or opening of the zona LAH on the clinical outcome of cleavage stage FET [5]. Among 122 pellucida by the embryologist prior to ET as an attempt to improve the consecutive procedures, 31 were in the control group (no AH), 34 probability of embryo implantation [1]. were in the AH group with 40μm ZP thinning, and 57 were in the AH group with 80μm ZP thinning. PR and IR were significantly higher in Methods of AH the 80 μm AH group as compared with control (40.3 vs 16.1%, P=0.03; 21.5 vs 7.5%, P=0.007, respectively). IR was significantly higher in the AH has been in use since the first report by Cohen in 1988 [2] and 80μm AH than the 40μm AH group (21.5 vs 9.4%, P=0.024). The has since evolved in terms of modality by which the ZP is artificially authors concluded that the greater size of ZP thinning may matter for thinned or opened. AH can be performed by mechanical, chemical, or PR and IR in cleavage stage FET [5]. laser-assisted means. When AH is performed to create an opening in the ZP, the procedure may be performed via the use of acidified The effect of the site of AH on outcomes Tyrode’s solution, partial zona dissection with a glass microneedle, laser photoablation or piezomicromaniupulation. When AH is Since two observational studies had shown that the natural hatching performed to thin and not breach the ZP, acidified Tyrode’s solution, site of the human blastocyst is near the inner cell mass (ICM) whereas proteolytic enzymes, or laser-assistance may be used [1]. that of the mouse is at the side opposite to the ICM [6,7], a prospective randomized study was conducted in order to study whether or not the The effect of the size of ZP breaching or thinning on AH choice of AH site is important to complete hatching. The authors of outcomes this preliminary report demonstrated a significantly higher rate of complete hatching when LAH was performed on thawed blastocysts Several studies have suggested that the larger size of ZP breaching near the ICM as compared to the side opposite to the ICM [8]. Ren et or thinning may confer a clinical benefit. In a study by Hiraoka et al., al. evaluated the effect of LAH site in vitrified-warmed blasts on 101 consecutive frozen-thawed embryo transfer procedures were clinical outcome of FET. A total of 16 women were randomized to a grouped into no Laser-Assisted Hatching (LAH) (n=30), LAH with 40 group with AH near site of ICM or to a group with AH at the site μm ZP opening (n=40), and LAH with 50% circumferential ZP opposite to the ICM. LAH was performed within 20-30 min after opening (n=31). Cleavage stage embryos were thawed and grown to blastocyst thaw once the ICM was detected. There was no difference in blastocyst stage in patients who had failed both fresh and frozen IR, PR, LBR, or monozyogotic twin rate between the two groups [9].

J IVF Reprod Med Genet Volume 2 • Issue 1 • 1000121 ISSN:jfiv an open access journal Citation: Kavoussi SK (2014) Assisted Hatching for In Vitro Fertilization-Embryo Transfer: An Update. J IVF Reprod Med Genet 2: 121. doi: 10.4172/jfiv.1000121

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The effects of AH on clinical outcomes endometriosis who had LAH performed for their embryos and 30 women with endometriosis who did not have LAH. There was no Unselected patients difference in PR (28.3% LAH group, 40% control group) or IR (17.8% LAH group, 19.4% control group) between groups. The authors The American Society for Reproductive Medicine (ASRM) concluded that AH does not improve outcome in women with committee opinion states that the existing literature does not support endometriosis [35]. the universal application of AH to all IVF cycles [1]. The majority of studies that have evaluated the effect of AH on the IR and PR of Multiple gestation unselected IVF patients have shown no increase in these outcome measures [10-16] and a recent systematic review and meta-analysis by Monozygotic twinning has been found to be more common in IVF Martins et al concluded that AH was unlikely to improve CPR in cycles and the incidence is increased in pregnancies following AH unselected fresh ET cycles whereas AH in unselected FET cycles was [36,37]. The recent review by Martins showed that AH increased efficacious [17]. multiple gestation rates [16]. The 2012 Cochrane Review found that there was low quality evidence showing a significant increase in Advanced maternal age multiple gestation rates per woman [25]. It has been theorized that ZP hardening may occur due to endocrine changes or the absence of lysins as a function of oocyte Conclusions aging in women of advanced maternal age. Although some studies AH is a technique that has been used in IVF laboratories for over 25 suggest benefit of AH in women of advanced maternal age, some show years. Several studies suggest that a larger size of artificial ZP opening/ no difference in IR and CPR [17-22]. Subgroup analysis of Advanced thinning as well as performing AH at a site close to the ICM may be Maternal Age (AMA) patients in the review by Martins showed no associated with a greater propensity for complete hatching. Universal benefit of AH in women of AMA who underwent fresh ET [16]. application of AH to all fresh IVF cycles is not recommended in accordance since the existing literature shows no difference in Thick ZP outcomes. Although LBR data may be insufficient at this time, AH A prospective, randomized, double-blinded, crossover study sought seems to increase IR and CPR in cases of prior implantation failure as to determine whether AH impacts clinical outcomes in women well as in FET cycles. Although there is some conflicting data about younger than 38 years whose embryos have a thickened ZP, defined as improved outcomes among women of advanced maternal age, data > 13 μm (n=121). Patients were randomized to a control group (no exists that supports AH in women 38 years of age or older. As AH) or group that had AH performed by acidic Tyrode’s solution. recommended by ASRM, each IVF program should assess their own There was no difference in IR, CPR, or LBR between groups; therefore, patient characteristics and determine whether or not AH may provide this study suggests that AH does not appear to provide benefit to benefit to certain subgroups of their patients. women under age 38 who undergo IVF [23,24]. References Prior implantation failure 1. Practice Committee of Society for Assisted Reproductive Technology In women with prior implantation failure, AH has been shown to (1988) The role of assisted hatching in in vitro fertilization: a review of significantly increase the CPR [16,25]. LBR was not proven to be the literature. A Committee opinion. Fertil Steril 90: S196-S198. increased; however, because most trials did not report LBR, there may 2. Cohen J, Malter H, Fehilly C, Wright G, Elsner C, et al. (1988) Implantation of embryos after partial opening of oocyte zona pellucida to have been insufficient data to draw conclusions regarding the effects of facilitate sperm penetration. Lancet 2: 162. AH on LBR. The ASRM Committee Opinion found that AH may be of 3. Hiraoka K, Fuchiwaki M, Hiraoka K, Horiuchi T, Murakami T, et al. benefit to women with > 2 failed IVF cycles [1]. 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